Key Points
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The physician must be familiar with and able to diagnose a wide range of infections that may be seen in the pediatric head and neck.
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The diagnosis of pharyngitis requires excellent history and physical documentation and appropriate culture and laboratory testing.
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The majority of children with sore throat have a viral pharyngitis that will not benefit from antibiotics or tonsillectomy.
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The diagnosis of pediatric airway infections requires astute clinical acumen to perceive the risk of airway obstruction and the possible need for rapid intervention.
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Viral croup is the most common obstructive airway infection in children.
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Supraglottitis and bacterial tracheitis are rare clinical entities, but recognition of their signs and symptoms is crucial for the prevention of morbidity and mortality.
Children may experience a variety of infections that involve the upper aerodigestive tract and surrounding structures that range from the benign, common upper respiratory infection (URI) to life-threatening supraglottitis. The astute clinician can often narrow the diagnostic possibilities by an accurate clinical history and targeted physical examination. Radiologic imaging, cultures, laboratory studies, and airway endoscopy may also be required for accurate diagnosis. The signs and symptoms of the various airway infections may have many similarities because the anatomic structures and tissues involved are close in proximity. Overlap in symptomatology occurs between viral and bacterial pharyngitis and infectious mononucleosis and also among epiglottitis, croup, and bacterial tracheitis. Therefore a thorough understanding of both common and rare diseases is necessary for accurate diagnosis and treatment as well as for prevention of morbidity and mortality. This chapter provides a thorough review of infectious processes that affect the upper aerodigestive tract.
Pharyngotonsillitis
Viral Pharyngitis
The classic “common cold” is the most frequent cause of URI in children. A multitude of offending viral pathogens have been implicated to cause pharyngitis; these include rhinovirus, influenza virus, parainfluenza virus, adenovirus, coxsackievirus, echovirus, Epstein-Barr virus, reovirus, and respiratory syncytial virus (RSV). Systemic viral disease from cytomegalovirus, measles, and rubella can also sometimes cause pharyngitis. URI-associated pharyngitis is usually preceded by other symptoms such as rhinorrhea and congestion, and it has mild symptomatology; patients complain of a mild to moderate sore throat, dysphagia, and hoarseness but typically do not have severe throat pain or odynophagia. Patients may have a low-grade fever with erythema of the pharyngeal mucosa and/or tonsillar hypertrophy without exudate. Adenovirus-associated pharyngitis typically is more painful, with higher fevers and conjunctivitis.
Herpangina caused by coxsackievirus is characterized by small vesicles with erythematous bases that become ulcers and spread over the anterior tonsillar pillars, palate, and posterior pharynx, sometimes with associated cutaneous rash ( Fig. 18-1 ). Hand-foot-and-mouth disease, most commonly caused by coxsackievirus A16, is associated with high fever and malaise followed by vesicular eruption in the mouth that causes oral and throat pain and a maculopapular rash or vesicles on the palms of the hands, soles of the feet, and buttocks. Children are highly contagious and should be kept away from other children until no longer symptomatic. Herpes simplex virus commonly causes the well-known “cold sore.” This virus can also cause exudative or nonexudative pharyngitis, mainly in older children and young adults. In younger children, the herpesvirus may induce gingivostomatitis.
Epstein-Barr Virus
Pharyngitis associated with Epstein-Barr virus (EBV), also known as infectious mononucleosis, is a common etiology of throat pain, especially in adolescents. The most common method of transmission is oral contact. Although younger children tend to be asymptomatic and have chiefly abdominal complaints, EBV induces the mononucleosis syndrome, which consists of fever, general malaise, headache, pharyngitis, dysphagia, and odynophagia. Exam findings may include normal-sized or hypertrophic tonsils, palatal petechiae, and large, tender cervical lymphadenopathy. Tonsils may have a green or gray exudate that cannot be distinguished clinically from streptococcal pharyngitis ( Fig. 18-2 ). Rash is rare and most commonly occurs in patients who have been treated with amoxicillin. Most patients have splenomegaly, and some have hepatomegaly. Atypical presentations of mononucleosis have been attributed to acute human cytomegalovirus infection.
Diagnosis of EBV is confirmed by laboratory studies. White blood cell counts typically range from 10,000 to 20,000/µl with a marked lymphocytosis and atypical lymphocytes. Serum transaminase, alkaline phosphatase, and bilirubin levels may all be elevated, although few patients manifest jaundice. The most commonly used diagnostic assay for mononucleosis is the heterophile agglutination test, which actually measures immunoglobulin M antibodies, which are not specific to EBV antigens but are produced by EBV-stimulated plasma B cells. However, only 40% to 60% of patients with infectious mononucleosis have a positive result within the first week after onset of the illness, and 80% to 90% have a positive result 1 month after onset. Children under 4 years of age may not develop the antibody. Young patients or those with atypical or persistent symptoms with a negative heterophile antibody may benefit from measurement of EBV-specific antibody titers. EBV-specific serologic assays have become the method of choice for confirmation of acute or convalescent EBV infection. Figure 18-3 shows the serologic response time.
Management of EBV mononucleosis is symptomatic. Recovery may take weeks, and pain control and airway management are important. Nonsteroidal antiinflammatory drugs (NSAIDs) are the mainstay of pain treatment. Antibiotics are not indicated; however, for patients who require treatment for concomitant bacterial infection, β-lactam antibiotics—particularly amoxicillin and ampicillin—are relatively contraindicated because of the risk of precipitating an EBV-associated rash. Patients with significant airway obstruction can benefit from corticosteroid treatment. If the obstruction is severe, a nasopharyngeal airway may be helpful, and rarely, a tonsillectomy or tracheotomy may be necessary. Other sequelae can occur that include splenic rupture and hematologic, ophthalmologic, dermatologic, cardiac, and central nervous system manifestations.
Streptococcal Tonsillitis-Pharyngitis
Group A β-hemolytic Streptococcus (GABHS) is the most common bacterial cause of acute pharyngitis. Of all children who present with acute pharyngitis, GABHS is implicated in 15% to 30% of patients. The public health importance of this infection lies in its common occurrence, risk of transmission, and potential for suppurative and nonsuppurative sequelae.
Acute streptococcal pharyngitis is a disease of childhood and adolescence with a peak incidence at 5 to 6 years of age and rare occurrences in children younger than 3 years. Outbreaks may arise in institutional settings such as camps and daycare facilities. Acute streptococcal pharyngitis most commonly presents with fever, sudden throat pain, and odynophagia. Associated symptoms include malaise, dysphagia, otalgia, headache, nausea, and abdominal pain. Signs include oropharyngeal erythema; enlarged tonsils, with or without exudate; swollen uvula; palatal petechiae; enlarged, tender cervical lymphadenopathy; and scarlatiniform rash. Children under 3 years of age have uncharacteristic symptoms that include mucopurulent rhinorrhea and excoriated nares without significant pharyngitis. Scarlet fever is a variation of GABHS pharyngitis associated with a descending rash, from the neck to the trunk and extremities, that develops 12 to 24 hours after the fever. In addition, patients may have enlarged papillae on the tongue with or without a white membrane (strawberry tongue).
The diagnosis of acute pharyngitis cannot be made reliably on clinical grounds alone because the manifestations of streptococcal and nonstreptococcal pharyngitis overlap so broadly. Accurate diagnosis is essential to limit transmission, improve recovery, reduce complications, and reduce use of antibiotics for viral illnesses. Children with symptoms strongly suggestive of a viral etiology—cough, rhinorrhea, hoarseness, and oral ulcers—do not require further testing. For all other children, the diagnosis of GABHS pharyngitis must be made by microbiologic tests.
Throat culture is the diagnostic test of choice for GABHS. Optimally obtained and processed, a single throat culture is 90% to 97% sensitive and 90% specific for GABHS growth. However, they can take 18 to 48 hours to produce results, and this time delay can cause issues with appropriate follow-up treatment. If GABHS is treated early in the clinical course, the period of communicability is reduced. Therefore, several rapid antigen detection tests for GABHS have been developed to detect streptococcal group A carbohydrate from swabbed material. Although the rapid detection tests are highly specific, they are not as sensitive as routine throat culture. Guidelines suggest that all children and adolescents who have a negative rapid antigen detection test result should undergo throat culture. In addition, these patients should also have a monospot and complete blood count to evaluate for other causes of sore throat.
Cultures alone cannot differentiate the acute and carrier states of GABHS. An estimated 20% of school-age children are chronic carriers, and approximately a third of household contacts of symptomatic GABHS patients are carriers. Recent guidelines advise that patients with frequent sore throat and positive studies for GABHS may either have frequent GABHS or are GABHS carriers with frequent viral pharyngitis. Screening for and prophylactic treatment of asymptomatic carriers is not generally recommended. However, it can be considered in four situations: 1) in patients with a history or family history of rheumatic fever; 2) during a community outbreak of rheumatic fever, poststreptococcal glomerulonephritis, or invasive GABHS infection; 3) when tonsillectomy is being considered; or 4) when symptomatic GABHS spreads among household members. The carrier state may be identified by serologic testing; a true infection is demonstrated by a positive throat culture result and at least a two-dilutional rise in the antistreptolysin-O titer, whereas carriers have no change in dilution titer. Serologic and culture evaluation combined with a careful history of symptoms and signs during episodes and response to antibiotics may help clarify true symptomatic GABHS from recurrent viral pharyngitis in carriers.
Penicillin or amoxicillin have traditionally been first-line agents for acute GABHS in most cases. For those who are penicillin allergic, a first-generation cephalosporin (as long as the reaction to penicillin is not anaphylaxis), clindamycin, clarithromycin, or azithromycin are first-line treatments. For most antimicrobials, a 10-day treatment course is recommended. Symptom management may be achieved with acetaminophen or NSAIDs; aspirin should be avoided, and steroids are not indicated. Antimicrobial failure in GABHS pharyngitis occurs, and penicillin failure may be as high as 40%; theories on its etiology include 1) a protective effect for GABHS by β-lactamase–producing bacteria in the tonsil, 2) lack of other bacteria that inhibit GABHS virulence, 3) poor penetration of the pharyngeal tissues by penicillin, and 4) antimicrobial resistance to penicillin. Recent data suggest that macrolides and cephalosporins may be more effective first-line therapy and that cephalosporins, clindamycin, and amoxicillin/clavulanic acid are all preferred for penicillin failures. Macrolide resistance because of the hypervariable region of the GAS M-protein gene has also been reported
Tonsillectomy may be considered in the treatment of children with recurrent throat infection. Current guidelines recommend the following criteria for tonsillectomy : well-documented clinical features for each episode (sore throat associated with fever >38.3° C, cervical lymphadenopathy, tonsillar exudate, or GABHS positive testing) and a frequency of seven episodes or more in the preceding year, five or more episodes in each of the preceding 2 years, or three or more episodes in each of the preceding 3 years. Children with less severe or frequent disease were unlikely to have long-term benefits from tonsillectomy. Other factors that inform decision making regarding surgery are the severity of each episode, how well infections have responded to medical therapy, and quality of life issues (e.g., number of school days missed). The guidelines also recommended tonsillectomy in children who have multiple antibiotic allergies or intolerance; periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA); or history of peritonsillar abscess. Children who undergo tonsillectomy for recurrent tonsillitis may have an increased risk of postoperative hemorrhage than those who undergo the procedure for obstructive symptoms.
Other Causes of Pharyngotonsillitis
Mycoplasma pneumoniae, Chlamydia pneumoniae, Treponema pallidum, Neisseria gonorrhoeae and N. meningitides, Arcanobacterium haemolyticum, Francisella tularensis, Yersinia enterocolitica. Helicobacter pylori, group B, C, and G Streptococcus, Fusobacterium species, and Peptostreptococcus species may all be rare causes of bacterial pharyngitis. Although thrush is quite common in infants, it typically is not painful, and candidiasis that causes significant throat pain is primarily found in the immunocompromised population.
The incidence of Corynebacterium diphtheriae infection has declined markedly since the introduction of diphtheria vaccination in the 1920s. This organism causes an early exudative pharyngotonsillitis with a thick pharyngeal membrane and produces a lethal exotoxin that can damage cells in distant organs. Infection can spread to the throat, tonsils, palate, ear, skin, and larynx with associated severe upper airway obstruction in a minority of cases. Only five cases have been seen in the United States since 2005; however, circulation of the bacteria has been documented in some segments of the U.S. population. In many developing countries, the disease is still endemic, and a major outbreak occurred in the Soviet Union in 1990.
C. diphtheriae is a gram-positive pleomorphic aerobic bacillus that can have a “Chinese character” appearance on Gram stain, but it is best identified by culture on tellurite media. C. diphtheriae must be distinguished from normal nasopharyngeal diptheroid flora because only toxigenic strains infected with a bacteriophage cause diphtheria disease. Early diagnosis and isolation of the patient is critical. Mortality rates range from 5% to as high as 20% in children under 5 years of age. Therapy includes administration of antitoxin, ideally within 48 hours of onset of disease, as well as antibiotic treatment, typically with erythromycin or penicillin G. Myocarditis and neurologic manifestations may occur. The disease is preventable with vaccination of children with either the diphtheria-tetanus toxoid or diphtheria-tetanus-pertussis vaccines.
PFAPA is the most common cause of pediatric recurrent fever. It consists of a prodromal phase of malaise, irritability, and fatigue that may precede the onset of fever. Fevers consistently last for 3 to 6 days, range from 38.5° to 41° C, and occur every 3 to 8 weeks with asymptomatic interval periods. Strict criteria include association of these periodic fevers with at least one of the following three symptoms: aphthous stomatitis, cervical adenitis, or pharyngitis. Other symptoms include headache, diarrhea, arthralgia, rash, chills, and abdominal pain. The typical age of onset is between 2 to 5 years of age. Laboratory tests may reveal a mild leukocytosis and elevated erythrocyte sedimentation rate. Some patients may experience spontaneous resolution of the disease after months to years, but the majority have persistent symptoms with increased length of intervals over time. The etiology of PFAPA is unknown, with no identified familial pattern or known mutations. The pathophysiology is believed to be immunologic dysregulation, proinflammatory cytokine activation, and antiinflammatory suppression. The differential for pediatric recurrent fever includes Hyper-IgD syndrome, cyclic neutropenia, and familial Mediterranean fever, among others. It is imperative that strict PFAPA criteria be utilized, preferably with infectious disease specialty input, to make appropriate management decisions.
NSAIDs are superior to acetaminophen for symptomatic treatment of PFAPA. Corticosteroids can markedly reduce symptoms but have been associated with shortened intervals between episodes. Cimetidine, an H 2 -receptor antagonist, has provided resolution in some patients. Inhibitors of chemokines and cytokines are in early pilot studies. Tonsillectomy has been successful in initially resolving the periodic fevers of PFAPA, but the possibility of relapse has been documented. A meta-analysis of studies of children who rigorously fulfilled PFAPA criteria demonstrated statistically significant improvement in chance of total resolution or longer intervals between episodes.
Complications of Tonsillitis
Complications of pharyngitis and tonsillitis are seen in GABHS disease and include both suppurative and nonsuppurative sequelae.
Nonsuppurative Complications
Rheumatic fever generally follows an episode of pharyngeal GABHS. Patients can present with polyarthritis, carditis, Sydenham chorea, and a truncal rash. Fortunately, acute rheumatic fever is now a rarity, with episodes occurring in 0.3% of streptococcal infection episodes. Patients with suspected cases of rheumatic fever should be referred to a cardiologist for complete work-up and treatment. Untreated disease can lead to rheumatic heart disease. Penicillin prophylaxis is essential for prevention of repeat streptococcal infections, and patients who are not compliant should have a tonsillectomy.
Poststreptococcal glomerulonephritis may be seen after both pharyngeal and skin infections, with an incidence of less than 1% of GABHS infections. Typically, an acute nephritic syndrome develops 1 to 2 weeks after a streptococcal infection. The infection is secondary to the presence of a common antigen shared by the glomerulus and the Streptococcus. Penicillin management may not decrease the attack rate, and no evidence suggests that antibiotic therapy affects the natural history of glomerulonephritis.
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) comprise a constellation of neurologic symptoms after GABHS infection. Diagnostic criteria include obsessive-compulsive disorder and/or tic disorder with onset between 3 years of age and puberty; an episodic course with abrupt onset of neuropsychiatric symptoms or dramatic exacerbations; a well-documented temporal relationship between symptom exacerbations and GABHS infections with culture confirmation; and an abnormal neurologic exam with motoric hyperactivity and adventitious movements without frank chorea. The etiology of PANDAS is believed to be an autoimmune phenomenon against neural cells, but this remains controversial. Treatment for PANDAS remains uncertain. Some research supports antibiotic prophylactic treatment of PANDAS cases to prevent neuropsychiatric symptom exacerbation Plasmapheresis and intravenous (IV) immunoglobulin are also being investigated.
Suppurative Complications
Suppurative complication of tonsillitis include cervical lymphadenitis, peritonsillar abscess, and parapharyngeal abscess.
Croup (Laryngotracheobronchitis)
Laryngotracheobronchitis, also commonly known as croup, is typically a viral disease of the larynx and trachea and is the most common infectious cause of stridor in children. An estimated 3% to 5% of children have at least one episode of croup during childhood. Children are most commonly affected when they are between 6 months and 3 years of age. There is a strong seasonal occurrence in late autumn and winter, but it can occur any time of year.
Parainfluenza viruses (types 1, 2, and 3) are implicated in the vast majority of children with croup (approximately 80%); however, a host of other viruses can cause croup symptoms, including influenza A and B, enterovirus, human bocavirus, coronavirus, rhinovirus, echovirus, reovirus, metapneumovirus, RSV, and adenovirus. Rarely, measles, varicella, herpes simplex viruses, and Mycoplasma pneumoniae are causes. Viral croup transmission occurs by direct contact and exposure to nasopharyngeal secretions. The incubation period is 2 to 6 days for parainfluenza virus type 1, and children may continue to shed the virus for up to 2 weeks. The viral infection initially involves the nasopharynx, followed by spread to the larynx and trachea, particularly the vocal folds and subglottis.
Characteristically, croup infections are preceded by 1 to 2 days of a nonspecific viral prodromal upper respiratory infection with low-grade fever. Classically, this evolves into a triad of hoarseness, stridor with a distinct expiratory component (seal-like barking cough), and varying degrees of upper airway obstruction. Children do not usually appear toxic. The duration of illness is usually 3 to 7 days, but it can persist for 2 weeks.
Croup may present with only mild symptoms of airway obstruction, but it can also cause severe, life-threatening airway obstruction. In evaluation, certain parameters are most important to consider: 1) whether stridor is inspiratory, expiratory, or biphasic; 2) respiratory rate; 3) chest retractions; 4) air entry into the chest by auscultation because it is decreased with severe obstruction; 5) anxiety or restlessness; 6) color or cyanosis; 7) oxygen desaturation by pulse oximetry; and 8) level of consciousness. The presence of biphasic stridor, retractions, high respiratory rate, oxygen desaturations, or altered consciousness indicates severe airway obstruction. Most children with croup have mild, self-limited disease; however, up to 30% require hospital admission for upper airway obstruction, and as many as 5% require intubation. The crucial factor in those with viral croup is the amount of swelling in the subglottic area. The subglottis is both the narrowest portion of the airway in children and is the only complete cartilaginous ring; therefore it is the most susceptible to obstruction by edema. Because stridor does not occur until airway obstruction is already significant, any further decrease in airway size caused by mucous plugging or crusting may lead to rapid and complete airway obstruction.
The diagnosis of croup is highly suggested by history and physical examination alone. Further evaluation may be achieved radiographically by high-kilovoltage anteroposterior and lateral films of the upper airway ( Fig. 18-4, A , and Fig. 18-5, A ). In croup, the anteroposterior view classically shows a “steeple sign” in the subglottic area (see Fig. 18-4, B ), whereas the lateral view is characterized by subglottic haziness (see Fig. 18-5, B ). The classic radiographic findings may be absent in 50% of patients and are also not pathognomic for croup.
Flexible fiberoptic laryngoscopy ( Fig. 18-6, A ) occasionally may be helpful in establishing the correct diagnosis of viral croup, but it must be performed with extreme caution to avoid inducing acute airway obstruction in children with moderate to severe obstructive symptoms. In patients with severe airway obstruction, an uncertain diagnosis, or risk factors for other airway pathology, direct laryngoscopy and bronchoscopy are warranted. Classic endoscopic findings of croup include edema and narrowing of the vocal folds and subglottis (see Fig. 18-6, B ). However, anatomic abnormalities cannot be completely assessed when endoscopic evaluation is performed during acute infectious illness.
A careful history is essential to develop appropriate differential diagnoses to croup. In the acute setting, the most important alternative diagnoses to consider are other life-threatening airway infections, particularly epiglottitis ( Table 18-1 ). In addition, the possible presence of an airway foreign body, thermal injury, or caustic ingestion must all be considered. Croup should be considered atypical if it occurs in infants younger than 6 months of age, lasts more than 7 days, is unusually severe, or does not respond to appropriate treatment; a wider differential should be considered in these atypical cases. Croup can be recurrent in approximately 5% of children, and studies have suggested that congenital subglottic narrowing and gastroesophageal reflux disease are the most common etiologies of recurrent croup. Asthma and allergy have also been implicated. Spasmodic croup, which involves nighttime acute episodes of crouplike symptoms without a preceding viral prodrome, is linked to allergic reactivity and gastroesophageal reflux disease. Other causes may be acquired subglottic stenosis; subglottic hemangioma, especially in infants; or other anatomic abnormalities. Further evaluation of children with recurrent or persistent croup may be warranted. Flexible laryngoscopy or a pH probe study may help identify reflux disease. Some advocate for complete endoscopic airway evaluation in all cases ; however, the vast majority of children do not require further treatment based on endoscopic findings. Risk factors for more severe disease include a history of intubation, age less than 1 year, and episodes that require hospital admission; these children should certainly undergo full endoscopic evaluation.
| Laryngotracheitis (Viral Croup) | Supraglottitis (Epiglottitis) | Bacterial Tracheitis | Retropharyngeal Abscess | |
|---|---|---|---|---|
| Age | 6 mo to 3 yr | 1 to 8 yr | 6 mo to 8 yr | 1 to 5 yr |
| Onset | Slow | Rapid | Rapid | Slow |
| Prodrome | URI symptoms | None or mild URI | URI symptoms | URI symptoms |
| Fever | Variable or none | High | High | Usually high |
| Hoarseness, barky cough | Yes | No | Yes | No |
| Dysphagia | No | Yes | Yes | Yes |
| Toxic appearance | No | Yes | Yes | Variable |
| Radiographs | Subglottic narrowing | Rounded enlarged epiglottis | Subglottic narrowing; diffuse haziness; Tracheal wall irregularities | Widened prevertebral space |
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